Genetic Variant KCNJ15:p.Ile88Ile (chr21-38299525-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_170736.3(KCNJ15):c.264C>T(p.Ile88Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,088 control chromosomes in the GnomAD database, including 478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 176 hom., cov: 32)

Exomes 𝑓: 0.011 ( 302 hom. )

Consequence

KCNJ15
NM_170736.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

14 publications found

Variant links:

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

KCNJ15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-1.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ15	NM_170736.3 link	c.264C>T	p.Ile88Ile	synonymous_variant	Exon 3 of 3	ENST00000398938.7	NP_733932.1	Q99712

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7 link	c.264C>T	p.Ile88Ile	synonymous_variant	Exon 3 of 3	1	NM_170736.3	ENSP00000381911.2		Q99712

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4751

AN:

152086

Hom.:

176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0801

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0876

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00745

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.0199

AC:

5001

AN:

251476

AF XY:

0.0176

show subpopulations

Gnomad AFR exome

AF:

0.0837

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.0966

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.00764

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0114

AC:

16719

AN:

1461884

Hom.:

302

Cov.:

AF XY:

0.0108

AC XY:

7826

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0826

AC:

2767

AN:

33480

American (AMR)

AF:

0.0106

AC:

474

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00333

AC:

AN:

26136

East Asian (EAS)

AF:

0.0667

AC:

2649

AN:

39700

South Asian (SAS)

AF:

0.00589

AC:

508

AN:

86256

European-Finnish (FIN)

AF:

0.0148

AC:

792

AN:

53418

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00747

AC:

8312

AN:

1112006

Other (OTH)

AF:

0.0176

AC:

1064

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1038

2076

3113

4151

5189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0312

AC:

4750

AN:

152204

Hom.:

176

Cov.:

AF XY:

0.0308

AC XY:

2290

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0799

AC:

3318

AN:

41524

American (AMR)

AF:

0.0137

AC:

210

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.0876

AC:

454

AN:

5180

South Asian (SAS)

AF:

0.00353

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0163

AC:

173

AN:

10594

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00745

AC:

507

AN:

68014

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

235

470

705

940

1175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0351

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.17

(source)

DANN

Benign

0.52

PhyloP100

-1.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over